Mems fluid pump with integrated pressure sensor for dysfunction detection

ABSTRACT

The invention relates to a pumping device including a pump ( 1 ) comprising—a pumping chamber ( 11 ) having a variable volume,—an inlet ( 2 ) communicating with the pumping chamber ( 11 ) and comprising a valve,—an outlet ( 5 ) communicating with the pumping chamber and comprising a valve,—an actuator adapted to change the volume of the pumping chamber,—a fluidic pathway comprising said inlet ( 2 ), said pumping chamber ( 11 ), said outlet ( 5 ) and a downstream line ( 7 ) situated downstream of the outlet valve,—a pressure sensor ( 4 ) for measuring the pressure between the valves of said pathway,—processing means for processing the received pressure data from the pressure sensor ( 4 ). The invention also covers a method for detecting a dysfunction in a pumping device as defined above.

TECHNICAL FIELD

The present invention relates to medical pumping devices and moreprecisely to the detection of dysfunctions in such devices.

BACKGROUND ART

The detection of dysfunctions, especially in medical devices, isimportant because the life of the patient may depend on properfunctioning of said devices. In case of infusion pumps, for example, thepotentially dangerous results of a failure are typically over-infusionor under-infusion of the drug into the patient.

Examples of dysfunctions are leaks, occlusions or presence of airbubbles in the pumping line.

State-of-the-art devices and methods for detecting dysfunctions inmedical devices are for instance disclosed in the following patentdocuments: US 2008/214979, EP 1 762 263 and U.S. Pat. No. 7,104,763.

When using certain drugs, such as insulin, the detection of occlusionmay be of particular importance since it is known that catheters mayocclude in numerous circumstances. Any such undetected occlusion mayresult in under-delivery of insulin because it remains undetected for along period of time. Current occlusion detection devices operate on thepiston of the syringe driver and need the building of high pressureinside the syringe before it is detected. Other occlusion detectorsconsist of pressure sensors situated after the pumping mechanism, on thepatient line, which have little sensibility because of e.g. thecompliance factor of the tubing line. In certain cases, the absence ofdetection of an occlusion at the onset of such occlusion result in ahigh glucose plasma concentration which may appear to the patient as aneed to increase its insulin level, resulting in a re-programming of thepump which may result, in the event the occlusion would be suddenlyreleased, in a larger quantity of insulin being suddenly administeredwith potential serious hazard to the patient.

SUMMARY OF THE INVENTION

The present invention offers an alternative and several improvementswith respect to state-of-the-art devices and methods.

In the invention, the detection of a dysfunction is based on themeasurement of the pressure in the pumping line and more preciselybetween the inlet and outlet valve of the pumping chamber.

Such a configuration offers a higher sensitivity as well as thepotential to detect several potential kinds of dysfunction.

More specifically the invention relates to a pumping device and to arelated method as defined in the claims.

According to a preferred embodiment of the invention, the inlet andoutlet of the pumping device include passive valves.

Advantageously, in the scope of the present invention (but not limitedthereto), a highly miniaturized infusion pump is considered. It is amembrane pump with two passive valves and is built using MEMStechnology. In contrast to syringe driven pumps, a silicon micro-pumpand preferably such micro-pumps are build from silicon, exhibits a morecomplex fluidic pathway and more precise control of the delivery whileincluding valves with a hard seat which may potentially be leaking inthe presence of particles.

A further preferred embodiment of the invention uses a pressure sensorwhich comprises a silicon membrane.

In another advantageous of the invention, the pressure sensor is placedbetween the pumping chamber and the outlet. This configuration offers amore precise control of the occlusion (including the potential to detectimmediately the onset of an occlusion during any pumping cycle) whileaddressing other purposes such as the detection of dysfunctions.

According to another preferred embodiment of the invention the systemcomprises a further pressure sensor.

This further pressure sensor may be preferably placed after the outletvalve, in the downstream line.

In some embodiments the system also comprises a temperature sensor.

The pressure sensor according to the invention may detect several typesof dysfunctions such as occlusions, air bubbles or infusion linedisconnection, generally during a very short time, i.e. a few seconds,when the pump is operating.

Another objective of the present invention is to precisely characterizeand/or monitor the characteristics of a pump during the manufacturingcycle to prevent any potential malfunction during use.

It is an objective for the manufacturing of any medical device, toensure the quality of each pump delivered to a patient. For any suchmedical product, the use of liquid is generally the only way to detect amalfunction of a pump. While such a test requires a long time andrepresents a significant cost, it is only possible if the entire fluidicline is changed after such test. In the event of a single use product(such as a disposable pump), it is not possible to change the fluidicline and therefore it is not possible to ensure a 100% testing of eachsuch pump manufactured, due to the liquid contamination during testing.Only a sampling of a batch can therefore be operated, such testing beingdestructive for the pumps considered, without insuring a 100% qualitycontrol.

The present also provides a system and a method which allows for acomplete control of each pump produced without resulting in acontamination of such pump. Such testing is preferably carried out withfiltered air and results in a detailed analysis of all importantparameters and safety characteristics in a very short period of time ofonly a few seconds—This way remainscompatible with the cost objectivesof such disposable pumps which need to remain very inexpensive tomanufacture.

DETAILED DESCRIPTION OF THE INVENTION

The invention will be better understood below with a detaileddescription including examples illustrated by the following figures:

FIG. 1 shows a cut view of a micro-pump according to a preferredembodiment of the invention;

FIGS. 2 and 3 illustrate a possible process of functional testing of thepump;

FIG. 4 illustrates another pressure profile of functional testingillustrating a dysfunction;

FIG. 5 illustrates a typical pressure profile during an actuation cycle;

FIG. 6 illustrates one preferred embodiment of an actuation cycle;

FIG. 7 illustrates pumping cycles of air and water;

FIG. 8 illustrates a typical evolution of the outlet pressure profile inpresence of an occlusion;

FIG. 9 illustrates a typical evolution of the inlet pressure profile inpresence of an occlusion

FIG. 10 illustrates an example of monitoring the outlet pressure duringan occlusion

FIG. 11 illustrates a pressure profile of a pump with a presence of aleakage

FIG. 12 illustrates a monitoring of pumping accuracy in the presence ofa decrease of flow rate;

FIG. 13 illustrates the relative variation of viscosity for atemperature change of 1° C.;

FIG. 14 shows how the definitions “peak” and “plateau” are used in thefigures.

Micro-Pump

The micro-pump 1 as illustrated in FIG. 1 is a highly miniaturized andreciprocating membrane pumping mechanism. It is made from silicon andglass, using technologies referred to as MEMS (Micro-Electro-MechanicalSystem). It contains an inlet control member, here an inlet valve 2, apumping membrane 3, a functional detector 4 which allows detection ofvarious failures in the system and an outlet valve 5. The principle ofsuch micro-pumps is known in the prior art, for example from U.S. Pat.No. 5,759,014.

FIG. 1 illustrates a pump with the stack of a glass layer (blue) as baseplate 8, a silicon layer (purple) as second plate 9, secured to the baseplate 8, and a second glass layer 10 (blue) as a top plate, secured tothe silicon plate 9, thereby defining a pumping chamber 11 having avolume.

An actuator (not represented here) linked to the mesa 6 allows thecontrolled displacement of the pumping membrane 3. A channel 7 is alsopresent in order to connect the outlet control member, the outlet valve5 to the outlet port placed on the opposite side of the pump.

Detector Principle

In the pump 1, the pressure inside the pumping chamber varies during apumping cycle depending on numerous factors, such as the actuation rate,the pressure at the inlet and the outlet, the potential presence of abubble volume, the valve characteristics and their leak rates.

According to the invention, it is the intend to monitor this pressureand to analyse the profile from one stroke to another in order to detectpotential dysfunctions.

Integrated Pressure Sensor

The pressure sensor 4 in the micro-pump 1 is made of a silicon membraneplaced between the pumping chamber and the pump outlet. It is located ina channel formed between the surface of the micro-pumps silicon layerand its top glass layer. In addition, it comprises a set of strainsensitive resistors in a Wheatstone bridge configuration on themembrane, making use of the huge piezo-resistive effect of the silicon.A change of pressure induces a distortion of the membrane and thereforethe bridge is no longer in equilibrium. The sensor is designed to makethe signal linear with the pressure within the typical pressure range ofthe pump.

The fluid is in contact with the surface of the interconnection leadsand the piezo-resistors. A good electrical insulation of the bridge isensured by using an additional surface doping of polarity opposite tothat of the leads and the piezo-resistors.

In another preferred embodiment of the invention the pressure sensorincludes an optical sensor. The sensor is preferably composed of onepart which is included in the pathway of the pump in-between the twovales and at least some optical parts placed outside of such fluidicpathway and able to measure the pressure detected inside the fluidicpathway. In another embodiment, the optical detection may also be placedentirely inside the pump while being able to measure the pressurein-between the two valves in the fluidic pathway. In another embodiment,an optical astigmatic element is located within the light path, i.e.between a flexible membrane in the pump and the optical sensor. Anychange of pressure in the pump induces a displacement of said membrane,a change of the light path and thus a change of the optical beam shapethanks to the presence of the astigmatic element. The optical sensor ispreferably sensitive to the shape of the optical beam, e.g. by includinga quadrant photodetector.

Functional Test

A first process that can be carried out with the pump according to thepresent invention is a functional test of said pump, e.g. at themanufacturing level.

While known functional tests using water last several hours and must beconsidered as destructive, the functional testing of the pump accordingto the present invention can be done in few seconds only with gas. Tothis effect, one uses the tiny dead volume of the pump for this test andthe integrated pressure sensor described above.

The principle of this functional test process is the following: anoverpressure is created inside the pump with the actuator and onemonitors the pressure decay in the pumping chamber which is directlyindicative of the leak rate. The maximum pressure is related to thecompression ratio of the pump and its self-priming capability. One canalso derive the valve pretension during a typical actuation cycle.

To generate the high pressure in the chamber one can control the outletvalve, e.g. pneumatically, in order to keep it closed during thecompression as shown in FIGS. 2 and 3.

More specifically FIGS. 2 and 3 represent the functional testing of thepump according to the present invention (in FIG. 2 the schematic processand in FIG. 3 the corresponding pressure profile).

During this test one monitors the signal of the detector whereby:

-   -   Pressure=0 indicates the rest position of the membrane    -   The pressure peak indicates the compression ratio of the        micro-pump    -   The pressure decay indicates the leakage rate of the valves    -   The pressure in the step 3 indicates the pretension of the        outlet valve    -   The pressure in the step 4 indicates the pretension of the inlet        valve

As illustrated (see for example the successive positions in FIG. 2),such test is started from a stand-by position. A pull step is firstexecuted which “aspirates” gas into the chamber from the inlet valve 2by movement of the membrane 3.

This is followed by a push step to empty the chamber of the gas, whilethe outlet valve 5 is open. In the next step, the outlet valve 5 isagain closed and one carries out a further pull step with the membrane3, and then in the next step one opens the outlet valve 5 to relief theunder pressure in the chamber.

Finally, with the outlet valve 5 closed, one executes a push step whichcorresponds to a compression step with the membrane 3. The chamber isnow under high pressure and the pressure decay (see FIG. 3) is anindication of the leakage rate of the valves.

The sensitivity of the method is very high due to the high pressuregenerated and the tiny volume involved.

A direct correlation between the compression ratio and the stroke volumeSV is found if one assumes that dead volume DV does not vary too muchthanks to a suitable process control during the initial manufacturing ofthe pump (e.g. by MEMS techniques).

FIG. 4 illustrates the pressure profile in case of a failure of thefunctional test.

In this case, the inlet valve of the pump is bonded (maintained closed)and moreover there is a leakage. These problem related to the inletvalve can be deducted by the large under pressure created during thepull move of the pump and the decay of the pressure after eachactuation. The leakage is indicated by the decay at the end of the highcompression step, at the end of the test cycle.

The same result can also be obtained during the functioning of the pumpin the event of a lack of fluid from the drug reservoir situated beforethe first valve (e.g. end of reservoir), in particular if using a closedsoft reservoir with no air vent.

In-Line Dysfunction Detection

As mentioned previously, the pressure inside the pumping chamber whilein fluid operation depends directly on various functional and/orexternal parameters, such as the pressure at the inlet or at the outlet,the actuation characteristics, but also micro-pump characteristics suchas the valve tightness, the actual stroke volume or the valvespre-tension.

A typical pressure profile during an actuation cycle with liquid isillustrated in FIG. 5.

Any change of this profile indicates a dysfunction of the pump or anincrease or decrease of pressure at the inlet or at the outlet (e.g. dueto a bad venting, an under-pressure or an over-pressure of a liquidreservoir, situated before the inlet valve or an occlusion after theoutlet valve).

In particular, the position of the plateau just after the first peak ofpressure measured inside the pumping chamber is a direct indication ofthe pressure at the outlet of the pump, after the outlet valve. Afterthe second peak we have a direct indication of the pressure at theinlet, before the inlet valve. The tightness of the valves and/or thepresence of bubbles induce a variation of the peak-to-peak amplitude andthe peak widths. The analysis of the pressure decay after each peak ofpressure indicates the leak rate of any of the valves.

The displacement of the membrane according to one embodiment of theinvention during the normal actuation cycle of the pump is shown in FIG.6.

According to such shown embodiment, the cycle is initiated by a firsthalf push movement of the membrane, leading to an increase of thepressure, an opening of the outlet valve and therefore an exhaust ofliquid.

The cycle is followed by a complete pull stroke in order to fill thepump (negative peak of pressure during the filling of the pump), andthen the pumping membrane is released and therefore comes back to itsrest position, inducing a second positive peak of pressure.

As said previously, the evolution of the pressure in the pumping chamberdepends directly on the actuation characteristics of the membrane.

It is also possible, for instance, to have a cycle starting with acomplete stroke, resulting from a full pull move first followed by afull push move. Such a cycle would typically be useful during a highspeed operation of the pump, e.g. during a bolus administration. With anactuation like this only two peaks can be measured, a negative peakfirst and then a positive one. The analysis can be correlated to theactuation profile and result in the same kind of dysfunction detection.

As a consequence, the following features can always be measured during apumping cycle by use of the pressure signal from the sensor situatedin-between the two valves and result in a direct indication of thefollowing characteristics:

-   -   1. The position of the plateau (+) just after a positive peak        (+) of pressure depends on the outlet valve pretension and the        pressure at the outlet of the pump after the outlet valve.    -   2. The position of the plateau (−) just after a negative peak        (−) of pressure depends on the inlet valve pretension and the        pressure at the inlet of the pump before the inlet valve.    -   3. The tightness of the valves and therefore the leaks are        correlated to the decay with time of the pressure after each        peak.    -   4. The relative positions of the two plateaus are also directly        correlated to the leak rate.    -   5. The height and the width of the peaks of pressure (positive        of negative) are directly correlated to the presence of air in        the pump.

Priming and Air Detection

The priming of the pump can also be monitored. The significantdifference of signal observed during the pumping of air and water isillustrated in FIG. 7.

As discussed previously, the peaks of pressure are modified by thepresence of air in the pump.

Air detection can be verified by:

-   -   1. Monitoring of the height of the peaks of pressure, resulting        in a possible alarm at a given threshold.    -   2. Monitoring of the widths of the peaks of pressure, resulting        in a possible alarm at a given threshold.    -   3. Monitoring of both heights and widths (via the integration of        the signal for instance) resulting in a definition of an alarm        threshold.

Outlet Pressure Monitoring

FIG. 8 shows a typical evolution of the pressure profile during anactuation in presence of pressure at the outlet of the pump after theoutlet valve.

Inlet Pressure Monitoring

FIG. 9 shows the same graph as FIG. 8, with pressure at the inlet.

Accordingly, during an actuation cycle a precise monitoring of bothinlet and outlet pressures can be obtained.

Such an inlet pressure monitoring can also help detecting the emptyingof a drug reservoir, when such reservoir is e.g. a soft reservoirwithout air-vent.

Occlusion Detection

The monitoring of the outlet pressure allows the occlusion detection asshown in FIG. 10.

There are several ways to analyse the curves reproduced in FIG. 10during an occlusion. One can for instance simply observe the shift ofthe pressure after each push move.

Occlusion detection can be done by

-   -   1. Monitoring of the position of the plateau (+) and definition        of an alarm threshold, typically when the position of the        plateau (+) becomes equal to the initial height of the peak (+).    -   2. Monitoring of the height and the width of the peak (+) with        an alarm threshold.

Such a pressure measurement inside the pump results in a very accurateand precise detection of an occlusion, since the measure is made insidethe fluid pathway and in correlation with other measured valuesindicative of other potential dysfunctions. Therefore, the resultingvalue measured can be correlated to the true occlusion or flowrestriction outside the pump and prevent any delay in informing thepatient of the need to either check the infusion line or change theinjection site.

Leakage Detection

FIG. 11 illustrates the pressure profile of a pump with a leakage:

The pressure relaxes very quickly towards the external pressure aftereach actuation. Without leakage, the pressure should relax towards thevalve pretension expressed in terms of pressure.

Accordingly, that valve pretension prevents free flow while alsoallowing leakage detection by the detection method of the presentinvention.

According to the notations given in the FIG. 14, leakage detection canbe done by:

-   -   1. Monitoring of the relative positions of the plateau (+) and        plateau (−) and definition of an alarm threshold.    -   2. Monitoring of the decay of pressure after each peak of        pressure and definition of an alarm using typical time constant.        Monitoring of the Pumping Accuracy for Close-Loop Application        e.g. with Insulin

With the invention, one is able to detect the failures such as valveleakage or air bubble that can affect the pumping accuracy within theaccuracy specifications.

FIG. 12 illustrates an example of the detector signal of a pump showinga nominal stroke volume and the same pump with particles that affect thepumping accuracy by 15%. The leakage induced by these particles can beeasily detected by analysing the difference of level before and afterthe large negative peak

This feature allows close-loop application by coupling the micro-pump toa glucometer thanks to the control of the insulin delivery accuracy viathe detector.

The detection here is similar to the leak detection, but the only focusis on leaks that affect the accuracy.

-   -   1. Monitoring of the relative positions of the plateau (+) and        plateau (−) and definition of an alarm threshold, typically when        they become equal after a typical time constant just after the        peak (+) and (−).    -   2. Monitoring of the decay of pressure after each peak of        pressure and definition of an alarm using typical time constant.

In the absence of such a precise monitoring of the accuracy of the pump,any such close loop system would result in increasing or decreasing theadministration of e.g. insulin because of the measured parameter (insuch case continuous monitoring of glucose level in e.g. the plasma orthe subcutaneous region, or the interstitial fluid), without taking intoaccount the alteration of the delivery of the pump. It is of upmostimportance, in the case of a close loop system, to ensure that thepumping parameters are well understood and controlled over time toprevent any wrong compensation which would be related to the pumpingmechanism and not the patient characteristics. In particular, an overinfusion of insulin because of an increase of glucose measurement couldpotentially result in a hazard to the patient if related to an unknowndefective pump or infusion set.

This is also particularly true when the glucose measurement is thereflect of a glucose plasma level within a 10 to 30 minutes delay. Insuch case, a defective pump would result in a wrong interpretation ofthe patient status, while any modification of the pump behaviour (e.g.infusion line occlusion relief or modification of the pumpingcharacteristics) would not be detected in time to prevent hazard to thepatient because of a such wrong interpretation.

Detection of the Infusion Line Disconnection

In some instances, the infusion line may become disconnected from thepump and a leakage may occur between the pump outlet and the infusionline connector. Leakage may also be present if the user connects anunapproved infusion line to the pump outlet. This results in a lowerfluidic resistance at the pump outlet because of such leakage. The smalldecrease of pressure at the pump outlet when the leak becomessignificant could be detected by using the integrated detector or byplacing a second pressure sensor in the micro-pump but after the outletvalve. The sensitivity of this sensor should be adapted to the pressureloss of the infusion line under normal conditions.

The high instantaneous flow rate of the pump due to its functioningprinciple is very favourable since the pressure drop in the infusionline is directly proportional to the flow rate.

If necessary, a specific test of tightness of the infusion line can bedone by generating for instance a stroke at higher speed for the liquidexhaust during the pump setting, preferably before the patient isconnected (e.g. during priming of the pump).

Additional Pressure Sensor at the Pump Outlet

The main detector is placed in the pumping chamber. Its reference portis communicating with the air space inside the pump system's housingwhich is at atmospheric pressure as long as the pump system is wellventilated. This sensor is also a relative pressure sensor. It could beuseful to get information about the patient's pressure, by placing anadditional pressure sensor after the outlet valve.

This additional pressure sensor is directly related to the patient'spressure. The two pressures sensors, the main one measuring the pressureinside the pumping chamber and the one measuring the pressure after theoutlet valve, should have the same reference port pressure. Comparingthe evolution of the two signals after a stroke is useful for thedetection of leaks within the pump, at the valve seats, or between theoutlet port of the pump and the patient (typically a bad connection ofthe patient set). This will be described in more details further in thepresent description.

Moreover, the difference of pressure between the two sensors just afterthe stroke, i.e. when there is no longer flow rate, is also a goodindication of the outlet valve tightness.

This additional sensor can be also used for the detection of abnormalpressure at the outlet port, including occlusion of the infusion set.

This additional sensor could also be calibrated if needed during thefunctional manufacturing testing, using gas as described above in thepresent specification

This additional pressure sensor could be easily integrated into the pumpchip by designing a second membrane for the pressure measurement: thepressure can be measured by using strain gauges in a Wheatstone bridgeconfiguration as used for the other pressure sensor inside the pump.Ideally the implantation doses for the strain gauges are the equivalentones to those of the main detector inside the pump. One can thereforeadjust the sensitivity if necessary by simply modifying the membranedimensions rather than the doses themselves.

The fluidic pathway between the outlet valve of the pump and the patientset should preferably be made not to trap air during the initial pumppriming.

Implementation of a Temperature Sensor for a Better Leak and AccuracyMonitoring Using the Additional Pressure Sensor

The present chapter discusses the reliability during the analysis of thesecond detector signal.

As mentioned previously, the width and the height of the peak ofpressure can be exploited in order to get information about thetightness of the downstream line between the pump and the patient. Onecan also propose qualitative criterions for these different features.

Moreover, the integral of the pressure versus time curve istheoretically proportional to the flow rate, for a given fluidicresistance. A change in this integral is a good indication of adysfunction, including bubbles, leaks . . . but also temperaturechanges.

P(t)−P(patient)=Rf×Q(t)

Where Rf is the fluidic resistance between the additional pressuresensor and the patient, Q(t) the instantaneous flow rate and P(t) thepressure measured by the additional sensor. Laminar flow is taken intoaccount and Rf is given by the Poiseuille's law. P(patient) is thepressure of the patient and also the pressure measured by the additionalsensor after the flow vanishes.

This sensor is also a good indicator for the pumping accuracy since wehave a direct access to the flow rate variation with time. Of course,for a given pumping system including the infusion set, the fluidicresistance will vary with temperature via the fluid viscosity(Poiseuille's law). Ideally this pressure sensor will also be coupled toa temperature sensor.

If liquid like water is used, the variation of the viscosity with thetemperature is well known and the correction of the signal can be donein order to no longer be temperature dependant. The dysfunctiondetection becomes now even more reliable.

The temperature sensor could be placed within the pump, for instance incontact with the liquid even if it is strictly not necessary thanks tothe small dimensions and good thermal conductivity of the pumpcomponents.

The thermal sensor could be a simple thermo-resistor (RTD or resistancetemperature detector) that shows a good sensitivity between 5 and 40° C.The Wheatstone bridge of the pressure sensors also shows similartemperature dependence and could serve for this purpose. A thermocouplecan also be incorporated in the pumping unit. Finally a semiconductortemperature sensor based on the fundamental temperature and currentcharacteristics of a diode or a transistor can be used.

If two identical transistors are operated at different but constantcollector current densities, then the difference in their base-emittervoltages is proportional to the absolute temperature of the transistors.This voltage difference is then converted to a single ended voltage or acurrent. An offset may be applied to convert the signal from absolutetemperature to Celsius or Fahrenheit.

FIG. 13 shows the relative variation of viscosity for a temperaturechange of 1° C. Since the fluidic resistance varies linearly with theviscosity, it become possible to directly access to the flow rateaccuracy which can be expected for a temperature sensor resolution of 1°C.: at 5° C. the max error induced by the temperature sensor over theflow rate accuracy is 2.8%. The sensor may also be designed in order tointroduce an error lower than the accuracy target for the flow rate.

The coupling of the pressure sensor at the outlet and the temperaturesensor could be used as a smart relative pulsed flow sensor which isefficient thanks to the small response time of the pressure sensor.

Absolute Flow Meter

For an absolute flow measurement, the fluidic resistance between theadditional pressure sensor and the patient should be known with a goodaccuracy. The patient's set shows typically large variation of fluidicresistance from one batch to another, by contrast to the fluidicresistance of a channel in the micro-pump. Care should also be taken tokeep the fluidic resistance of the patient's set very low by contrast tothe fluidic resistance of the outlet channels within the micro-pump.

The fluidic resistance Rf given above can be controlled with an accuracycompatible with an absolute flow measurement.

According to the previous discussion, the flow measurement is valid aslong as the fluidic resistance of the patient's set remains small, i.e.there is no occlusion of the fluidic line.

The flow rate at the outlet of the micro-pump is measured. Any leakageafter the additional pressure sensor (connector . . .) will induce achange of the signal shape of both detectors, but the flow measuredremains correct.

The flow monitoring is also a very powerful feature but we still needinformation of both detectors for a correct interpretation of the flowdata.

During the additional pressure sensor calibration, it is also possibleto make a calibration of the integral of the pressure signal which isproportional to the flow rate (typically by using a commercial flowmeter placed in series with the outlet of the pump). Here again careshould be taken of not introducing a large fluidic resistance at theoutlet during the test.

The invention is of course not limited to the examples discussed andillustrated above but cover any embodiment falling under the scope ofthe claims.

1. Pumping device including a pump (1) comprising a pumping chamber (11)having a variable volume, an inlet (2) communicating with the pumpingchamber (11) and comprising a valve, an outlet (5) communicating withthe pumping chamber and comprising a valve, an actuator adapted tochange the volume of the pumping chamber, a fluidic pathway comprisingsaid inlet (2), said pumping chamber (11), said outlet (5) and adownstream line (7) situated downstream of the outlet valve, a pressuresensor (4) for measuring the pressure between the valves of saidpathway, processing means for processing the received pressure data fromthe pressure sensor (4).
 2. Pumping device according to claim 1 whereinthe pressure sensor (4) is structurally adapted to be used for detectingocclusions in the downstream line (7).
 3. Pumping device according toclaim 1 wherein the pump is a micro pump with the volume of the pumpingchamber (11) comprised between 10 nl and 100 μl.
 4. Pumping deviceaccording to claim 1 comprising a pumping membrane (3), functionallylinked to said actuator, which is adapted to change the volume of saidpumping chamber (11) and wherein at least one said valves is a checkvalve.
 5. Pumping device according to claim 1 wherein at least one valveincludes pretension means that are activated at least during operationof part of the pumping cycle.
 6. Pumping device according to claim 1wherein at least one valve can be further externally controlled. 7.Pumping device according to claim 1 wherein the pressure sensor (4)comprises a flexible membrane.
 8. Pumping device according to claim 4wherein the pumping membrane (3) is made of a semiconductor material,and wherein a strain gauge is implanted or diffused onto the membrane(3).
 9. Pumping device according to claim 4 comprising an optical sensorwhich is adapted to monitor the deflection of the pumping membrane (3).10. Pumping device according to claim 9 comprising an astigmatic opticalelement between the pumping membrane (3) and the optical sensor. 11.Pumping device according to claim 1, comprising at least one furtherpressure sensor.
 12. Pumping device according to claim 11 wherein saidfurther pressure sensor is positioned in the downstream line. 13.Pumping device according to claim 1 comprising a flow restrictor in thedownstream line.
 14. Pumping device according to claim 11 wherein saidfurther pressure sensor is positioned between the outlet valve and theflow restrictor.
 15. Pumping device according to claim 1 furthermorecomprising a temperature sensor.
 16. Method for detecting at least onedysfunction in an infusion assembly which includes a pumping device asdefined in claim 1, the method comprising the measurement of thepressure in the fluidic pathway during pumping, the processing of theresulting pressure values and the provision of a functioning statusbased on the processed pressure values.
 17. Method according to claim 16for a pumping mechanism which is achieved through repetition of pumpingcycles; each of said pumping cycle including at least one suction phaseduring which the volume of the pumping chamber is increased and thepressure is thus decreased, and also at least one discharge phase duringwhich the volume of the chamber is decreased and the pressure is thusincreased; the pumping chamber volume returning to its initial size atthe end of the cycle.
 18. Method according to claim 17 wherein each ofsaid pumping cycle further includes at least one stationary phase, afterthe discharge phase and/or after the suction phase, during which thevolume of the pumping chamber does not change, both valves being closedand the pressure in the pumping chamber is thus essentially constant butdiffers from the pressure at the inlet or at the outlet.
 19. Methodaccording to claim 16 wherein the dynamic pressure is measured duringeach phase of a pumping cycle.
 20. Method according to claim 16 fordetecting at least one of the following dysfunctions: Occlusion,leakage, air bubbles, bad connection, pumping non-accuracy, malfunctionof the actuator, emptying of a drug reservoir.
 21. Method according toclaim 16 wherein the processing of the resulting pressure valuesincludes a comparison between the measured pressure values among eachothers and/or reference pressure values.
 22. Method according to claim16 including the determination of at least one of the pressure change,the maximum pressure, and/or the minimum pressure during at least onephase of a pumping cycle.
 23. Method according to claim 16 including thedetermination of the time to achieve a predefined pressure during apumping cycle.
 24. Method according to claim 18 for detecting at leastone of the following dysfunctions during at least one stationary phase:leakage, bad connection and pumping non-accuracy by measuring the rateof pressure change.
 25. Method according to claim 24 wherein leakage,bad connection and/or pumping non-accuracy is detected when at least twomeasured pressure values of the stationary phase after the discharge andthe suction phases become equal.
 26. Method according to claim 16 fordetecting downstream occlusions by measuring the maximum pressure duringthe discharge phase.
 27. Method according to claim 18 wherein anocclusion is detected if the value of the pressure during the stationaryphase after the discharge phase is not decreased, at least by a certainpercentage or value, with respect to the maximum pressure during thedischarge phase.
 28. Method according to claim 16 for detection of airin the pump device by measuring the pressure at least during onedischarge phase and/or one suction phase.
 29. Method according to claim28 wherein air in the pump is detected if a pressure response during thecompression and/or depression cycle shows a substantially lower peakand/or wider peak than a normalized pressure response.
 30. Methodaccording to claim 16 including a leak test which is enhanced bygenerating a high pressure in the pumping chamber, e.g. by closing theoutlet valve by external means and by compressing the volume in thepumping chamber.
 31. Method according to claim 30 wherein after creatingan overpressure in the pumping chamber, a maximum of pressure and apressure decay are monitored for detecting leakage rate, compressionratio and/or self-priming capability of the pump, valve pretensions,malfunction of the actuator and/or stroke volume.
 32. Method accordingto claim 16 for measuring the pulsed flow rate of a pumping device, saidmethod comprising the measurement of the pressure in the downstream lineusing constant sampling intervals and the processing of the resultingpressure values.
 33. Method according to claim 16 for detecting, byusing jointly a pressure sensor in the pump and a pressure sensor in thedownstream lime, at least one of the following parameters: Flow rate,occlusion, leakage, air bubbles, bad connection, pumping non-accuracy,malfunction of the actuator.
 34. Method according to claim 33 forfurthermore measuring the leak rate of the valve located between thepressure sensor in the pump and the further pressure sensor in thedownstream line, the method comprising the measurement of the pressuresdownstream and upstream of said outlet valve and a comparison betweenthe measured pressure values among each others and/or according toreference pressure values.